Findings
Human Factors Engineering (HFE) and Usability Engineering (UE) are fundamental for medical device safety and effectiveness. The HFE/UE process focuses on the interactions between people and devices, considering three major components: device users, device use environments, and the device user interface. The most important goal of this process is to minimize use-related hazards and risks. The FDA's HFE requirements are derived from the Quality System Regulation (QSR), specifically relating to Design Input (needs of the user and patient) and Design Validation (conformance to defined user needs). If risk analysis shows that use errors could lead to serious harm, HFE is explicitly required and must be submitted in premarket submissions (PMA, 510(k)).

Recommendations
Manufacturers should follow HFE/UE processes throughout the device development to improve design and minimize potential use errors. This involves an iterative process that runs parallel to product development. Key steps include:
User Research: Understand the intended users (e.g., professionals, patients, lay caregivers) and their characteristics (e.g., physical, cognitive abilities, experience).
Risk Analysis: Focus on potential use errors and identify critical tasks where errors could result in serious harm.
Formative Evaluation: Conduct evaluations during development to generate ideas for test scenarios, identify dangers early, and gather input for user interface improvements.
Design for Safety: Apply the hierarchy of risk control, prioritizing inherently safe design and protective measures (alarms, warnings) over instructions and training.
Usability Validation Testing: Conduct final summative testing with representative users under simulated real-world use conditions to demonstrate the device can be used safely and effectively.

Regulatory Considerations
The FDA recommends that manufacturers submit human factors data in premarket submissions for devices where risk analysis indicates that use errors could result in serious harm. The FDA has provided guidance on the content that should be included in these submissions, such as descriptions of intended users, use environments, user interface, risk analysis of use-related hazards, and results of validation studies. Manufacturers should also continue to monitor user interactions through postmarket surveillance and adverse event reporting.

Findings
An accessory is defined as a finished device that supports, supplements, or augments the performance of a parent device.
Accessories are classified based on their individual risk profiles when used with parent devices, which may differ from the classification of the parent device.
The De Novo process can be used for new accessory types with no existing classification, enabling lower-risk accessories to be classified in Class I or II.
Articles not specifically intended for use with a medical device (e.g., generic batteries or monitors) are not considered accessories unless labeled or promoted for such use.
FDA encourages using pre-submission requests to obtain feedback before submitting Accessory Requests or De Novo classifications.

Recommendations
Determine whether an article qualifies as an accessory by evaluating its intended use with a parent device based on labeling and promotional materials.
Evaluate the risks associated with the accessory when used as intended with its parent device, considering both unique and parent-related risks.
Use the Accessory Request process for new or existing accessories to propose appropriate classifications, supported by evidence of risk profiles and proposed regulatory controls.
Submit De Novo requests for new accessory types lacking existing classifications, providing data on performance, risks, and mitigation measures.
Include clear and comprehensive labeling for accessories, specifying compatibility and performance with identified parent devices.

Regulatory Considerations
Classification of accessories should reflect their risks and required controls, independent of their parent device classification.
Accessories categorized as Software as a Medical Device (SaMD) must meet the same risk-based classification framework applied to other medical devices.
Manufacturers can request reclassification or exemption from 510(k) requirements for previously classified accessories through applicable FDA mechanisms.
FDA must respond to Accessory Requests for existing accessory types within 85 days and De Novo requests within 120 days, as specified in the FD&C Act.
The Paperwork Reduction Act governs the submission of accessory classification requests, requiring compliance with established timelines and documentation requirements.

Findings
There is uncertainty regarding the regulatory acceptability of data collected from wearable devices.
There is a lack of specific regulatory guidance on implementing wearables in clinical trial protocols.
The need for evidence to demonstrate the appropriateness and clinical relevance of new endpoints derived from wearable data.

Recommendations
Identify essential properties of fit-for-purpose wearables and propose evidence needed to support their use.
Extend the FDA's definition of a PerfO to include unsupervised settings.
Ensure that any wearable device adheres to basic properties important to clinical trials, such as source data control, traceability, and security.
Provide evidence supporting the reliability, validity, and interpretability of data generated by wearable devices.

Regulatory Considerations
Market clearance/certification is not a requirement for device selection in clinical trials if evidentiary considerations are satisfied.
The need for a robust framework for adopting wearables in regulatory trials despite the lack of specific guidance.
The evidence needed to support a device and its endpoint depends on the ultimate use of the endpoint.

Findings
Clinical Evaluation Components: Valid Clinical Association: Demonstrates that the SaMD's outputs are clinically meaningful and relevant to the intended healthcare condition. Analytical Validation: Confirms that the SaMD processes input data accurately and reliably to produce the intended output. Clinical Validation: Assesses whether the SaMD achieves its intended purpose in the target population.
Lifecycle Management: Clinical evaluation is an ongoing process that spans pre-market development and post-market monitoring.
Post-market data collection supports continuous improvement, including refining or expanding the SaMD’s intended use.
Risk-Based Approach: The depth and independence of clinical evaluation depend on the SaMD's risk categorization, with higher-risk categories requiring more rigorous oversight and validation.
Real-World Evidence: SaMD manufacturers are encouraged to use real-world performance data for iterative learning, ensuring alignment with evolving clinical needs.
Independent Review: High-risk SaMD (e.g., those used for critical diagnoses or treatments) benefit from independent evaluation to manage bias and validate clinical evidence.

Recommendations
Pre-Market: Generate evidence through clinical trials, literature reviews, and secondary data analysis to demonstrate valid clinical association and analytical validation.
Use a risk-based framework to determine the rigor of clinical evaluation.
Post-Market: Leverage real-world performance data for continuous improvement and risk management.
Monitor safety, effectiveness, and user interactions, adapting the SaMD definition statement as needed.
Regulatory Submissions: Provide a clear SaMD definition statement, including intended use and core functionality.
Include comprehensive validation data, particularly for high-risk SaMD.
Independent Review: Engage third-party reviewers for high-risk SaMD to enhance transparency and confidence in clinical evaluation.
Quality Management: Integrate clinical evaluation activities into the organization’s quality management system to ensure consistency and compliance.

Regulatory Considerations
SaMD manufacturers must comply with jurisdiction-specific pre-market and post-market requirements, such as informed consent for clinical trials and regulatory submissions for significant changes.
Changes to the SaMD’s intended use or performance measures, based on post-market data, may necessitate updated regulatory approvals.
Independent review requirements vary by jurisdiction but are critical for higher-risk SaMD categories.

Findings
Many researchers, patients, and other stakeholders lack clarity about when and how to engage as partners within the clinical research process . There is a clear need for guidance on creating meaningful stakeholder partnerships in patient-centered clinical comparative effectiveness research . Engaging patients, caregivers, and other health care stakeholders as partners in planning, conducting, and disseminating research is a promising way to improve clinical decision making and outcomes .

Recommendations
The PCORI Engagement Rubric provides a framework for operationalizing engagement to incorporate patients and other stakeholders in all phases of research . The Rubric includes principles of engagement, definitions of stakeholder types, key considerations for planning, conducting, and disseminating engaged research, potential engagement activities, and examples of promising practices from PCORI-funded projects . PCORI encourages applicants, awardees, and others to apply the rubric to shift the research paradigm from one of conducting research on patients as subjects to a pursuit carried out in collaboration with patients and other stakeholders to better reflect the values, preferences, and outcomes that matter to the patient community .

Regulatory Considerations
The paper does not provide specific regulatory considerations. The PCORI Engagement Rubric was designed to illustrate opportunities for engagement to researchers interested in applying for PCORI funding and to patients and other stakeholders interested in greater involvement in research .

Findings
HFE/UE is essential for identifying and mitigating use-related risks that could compromise device safety or effectiveness.
Preliminary analyses, such as task and fault tree analyses, help identify critical tasks and use-related hazards early in device development.
Human factors validation testing must represent realistic use scenarios, include diverse user populations, and focus on critical tasks with potential for serious harm.
Residual risks that remain after validation testing must be justified in terms of the device's overall benefits and risk management measures.
Effective risk management prioritizes design modifications over labeling or training as the primary method for addressing use-related hazards.

Recommendations
Incorporate HFE/UE into all stages of device development to address use-related hazards through design improvements.
Conduct comprehensive risk analyses to identify and prioritize critical tasks that may lead to serious harm if performed incorrectly.
Design human factors validation testing to reflect real-world conditions and involve representative user populations.
Address use-related risks primarily through design modifications, with labeling and training as secondary measures.
Submit detailed HFE/UE documentation in premarket applications to facilitate FDA review and approval.

Regulatory Considerations
Submit human factors validation testing data as part of premarket applications for devices where use-related errors could result in serious harm.
Risk management processes must align with standards such as ANSI/AAMI/ISO 14971 and IEC 62366, ensuring comprehensive hazard identification and mitigation.
Conduct additional validation testing if modifications to a marketed device impact user interactions or introduce new risks.
For actual-use testing, ensure compliance with Investigational Device Exemption (IDE) requirements where applicable.
Manufacturers should maintain detailed records of HFE/UE processes, which must be available for FDA review upon request.

Findings
Traditional DMD endpoints focus on ambulation, excluding non-ambulatory patients and limiting trial inclusivity.
Accelerometer technology offers objective, real-world data collection, reducing the burden on patients and caregivers while enabling longitudinal assessment.
"Total arm movement" as a concept of interest captures meaningful functional activities across ambulatory and non-ambulatory populations.
Challenges include ensuring compliance with device use, minimizing variability from external factors (e.g., seasons, school schedules), and correlating data with meaningful treatment effects.
Continuous collaboration and data sharing among stakeholders, including regulators and technology manufacturers, is essential for endpoint development.

Recommendations
Define meaningful activities of daily living (ADLs) for DMD patients and correlate them with accelerometer-derived metrics, such as total arm movement.
Validate accelerometer data through natural history studies, cross-sectional analyses, and correlation with existing DMD-specific measures (e.g., DMD Upper Limb PROM).
Optimize measurement schedules to balance patient compliance with longitudinal data collection needs, focusing on real-world settings.
Collaborate with regulators to align endpoints with evidentiary requirements for clinical trials, ensuring their relevance and applicability.
Develop frameworks for continuous data sharing and standardization to streamline endpoint validation and regulatory acceptance.

Regulatory Considerations
Validate the endpoint to reflect meaningful treatment effects and ensure alignment with regulatory standards for phase III trials.
Address variability in data collection due to environmental or behavioral factors to enhance reliability and applicability.
Develop methodologies to correlate accelerometer-derived metrics with clinically meaningful outcomes and validated DMD measures.
Engage regulators early to obtain feedback and ensure endpoints meet the criteria for use in pivotal trials.
Explore the potential for composite endpoints combining accelerometer data with PROs to provide a comprehensive view of patient outcomes.

Findings
Existing PROs for HF, such as KCCQ and MLHFQ, are insufficiently sensitive and rely on subjective assessments.
Accelerometer technology offers objective and continuous real-world data that may better capture patient activity and health.
Novel endpoints must be validated through analytical and cross-sectional studies, correlating "time walking" with HF severity and clinical outcomes.
Developing and validating these endpoints is more feasible for patients with NYHA class II/III HF due to their moderate activity levels.
Future refinements and central databases of accelerometer data will enhance endpoint development and application.

Recommendations
Use accelerometer-derived metrics, such as "time spent walking per day," as novel endpoints to complement traditional clinical measures.
Validate novel endpoints through controlled and real-world studies, including correlating them with existing HF measures and clinical outcomes.
Include accelerometer endpoints in exploratory analyses within ongoing HF trials to gather supportive data without requiring regulatory submission.
Establish data standards and centralized databases for accelerometer-derived endpoints to streamline future development.
Collaborate across stakeholders, including patients, clinicians, investigators, and regulators, to align endpoint development with real-world applicability and regulatory requirements.

Regulatory Considerations
Demonstrate that accelerometer-derived endpoints reflect meaningful changes in patient health and correlate with established HF measures.
Validate endpoints in diverse patient populations and real-world settings to support generalizability and regulatory acceptance.
Address missing data and potential biases in accelerometer readings during endpoint analysis and validation.
Ensure endpoints align with regulatory trial design and analysis standards, including blinding and pre-specified analytical plans.
Develop frameworks for incorporating accelerometer-based endpoints into regulatory submissions alongside traditional clinical outcomes.

Findings
Cybersecurity risk management is a shared responsibility involving manufacturers, healthcare organizations, and IT vendors.
Proactive measures, such as threat modeling and vulnerability scanning, are critical to mitigating risks throughout the device lifecycle.
Cybersecurity routine updates and patches are generally considered enhancements and are not subject to 21 CFR Part 806 reporting unless risks are uncontrolled.
Participation in ISAOs is encouraged to foster collaboration and timely sharing of vulnerability and threat information.
Effective remediation plans must address vulnerabilities promptly, with appropriate reporting and user communication.

Recommendations
Monitor cybersecurity signals from diverse sources, including ISAOs, CERTs, and internal investigations, to identify and assess vulnerabilities.
Establish a robust risk management program incorporating the NIST Cybersecurity Framework to address risks from design to obsolescence.
Use tools like the Common Vulnerability Scoring System (CVSS) for assessing exploitability and prioritizing remediation efforts.
Communicate vulnerability and mitigation strategies clearly to users, ensuring they understand risks and appropriate controls.
Report uncontrolled vulnerabilities to FDA under 21 CFR Part 806, unless certain conditions are met (e.g., timely remediation, participation in ISAOs).

Regulatory Considerations
Cybersecurity routine updates addressing controlled risks are not typically subject to FDA reporting requirements under 21 CFR Part 806.
Uncontrolled risks must be remediated promptly, with detailed reporting to FDA, unless alternative measures like ISAO participation and mitigation plans are in place.
Class III devices with periodic reporting requirements must include cybersecurity-related updates and vulnerabilities in annual PMA reports.
Manufacturers must document their risk assessments, remediation plans, and user communications to demonstrate compliance with 21 CFR Part 820.
Threat detection and forensic capabilities should be built into device designs to support postmarket monitoring and risk mitigation.

Findings
The process of obtaining Informed Consent (IC) involves providing adequate information to facilitate comprehension and must allow subjects the opportunity to ask questions, continuing throughout the research. Electronic Informed Consent (eIC) systems, which can use various electronic media, are increasingly used to supplement or replace paper-based IC processes. The eIC process may be conducted on-site or remotely, but the legal responsibility for obtaining consent cannot be delegated to the electronic system. For FDA-regulated clinical investigations, electronic signatures must comply with 21 CFR Part 11 to be considered equivalent to a handwritten signature.

Recommendations
Presentation & Comprehension: eIC information should be easy to navigate, convey information in understandable language, and may use interactive electronic-based technology (e.g., diagrams, video) to facilitate comprehension. Optional questions can be used to assess a subject's understanding of key study elements.
Remote Consent: If consent is obtained remotely, the electronic system must include a reliable method to verify the identity of the subject (e.g., official identification, biometric methods).
Signature & Documentation: Electronic signatures are permitted and can be created using methods like biometrics or username/password, provided they are uniquely linked to the individual. The subject must be given a copy of the signed eIC, which can be electronic or paper.
Privacy & Security: The eIC system must be secure with restricted access and include methods to ensure confidentiality of subject information. If HIPAA applies, information must be encrypted unless otherwise documented.

Regulatory Considerations
IRB Responsibility: IRBs must review and approve all eIC materials and any subsequent amendments, including optional comprehension questions and the usability of the eIC materials. IRBs must maintain records (electronic or hard copy) of the approved versions of the eIC materials.
Submissions & Inspection: For IDE applications, copies of all eIC materials must be submitted to the FDA. During inspections, investigators must have site-specific signed eICs, amendments, and materials available (electronic or paper) for FDA review.
HIPAA: HIPAA authorizations may be obtained electronically, provided the signature is legally valid, and a copy must be provided to the subject.

Findings
The FDA's increasing commitment to patient-focused drug development (PFDD) and patient engagement in translational research presents a significant opportunity to improve the clinical trials enterprise and enhance participation by patient groups . Patient groups can play important roles in improving the entire therapeutic development enterprise, from study endpoint selection that reflects outcomes meaningful to patients, to recruitment and retention in clinical trials, and more effective postmarketing safety . However, there is a lack of clarity about how, when, and by whom patients or patient groups should be engaged during the therapy development process, and which patients or patient groups should be engaged . Metrics by which the value of such engagement, in terms of regulatory and market success, might be measured are also lacking .

Recommendations
PFDD and patient engagement in research should be considered an effort to extend the benefits of incorporating patient insight and experiences, as well as desires and preferences, from bench to bedside and back . The therapeutic development process should meaningfully engage patients throughout, though specific guidance on implementation methods is needed .

Regulatory Considerations
The paper does not provide specific regulatory considerations or recommendations. The focus remains on identifying the opportunity and gaps in current patient engagement approaches rather than detailing regulatory pathways or compliance requirements.